Dijk S N, Francis P T, Stratmann G C, Bowen D M
Miriam Marks Department of Neurochemistry, Institute of Neurology, London, England, U.K.
J Neurochem. 1995 Nov;65(5):2165-9. doi: 10.1046/j.1471-4159.1995.65052165.x.
Physostigmine, the acetylcholinesterase inhibitor (0.3 mg/kg, i.m.), increased extracellular glutamate but not aspartate concentrations in the striatum of anaesthetised rats, determined using microdialysis and HPLC. The rise was both tetrodotoxin and calcium dependent. In contrast, neither physostigmine (10 microM) added to the perfusion fluid nor vehicle (injected intramuscularly) affected amino acid concentrations. To obtain evidence that the action of acetylcholine was to modulate positively cortical pyramidal neurone activity via the M1 receptor, the selective M1 agonist PD 142505-0028 (10 microM) was topically applied to the frontal cortex. Like physostigmine, PD 142505-0028 rapidly increased glutamate but not aspartate concentrations in the striatum. Moreover, the effect of intramuscular physostigmine was blocked by a topically applied M1 antagonist. These new data add to our hypothesis that cholinomimetics increase pyramidal neurone function.
毒扁豆碱，一种乙酰胆碱酯酶抑制剂（0.3毫克/千克，肌肉注射），可增加麻醉大鼠纹状体细胞外谷氨酸盐浓度，但不影响天冬氨酸盐浓度，这是通过微透析和高效液相色谱法测定的。这种升高既依赖于河豚毒素，也依赖于钙。相比之下，添加到灌流液中的毒扁豆碱（10微摩尔）和溶剂（肌肉注射）均未影响氨基酸浓度。为了获得乙酰胆碱通过M1受体正向调节皮层锥体神经元活动的证据，将选择性M1激动剂PD 142505-0028（10微摩尔）局部应用于额叶皮层。与毒扁豆碱一样，PD 142505-0028能迅速增加纹状体中谷氨酸盐而非天冬氨酸盐的浓度。此外，局部应用的M1拮抗剂可阻断肌肉注射毒扁豆碱的作用。这些新数据支持了我们的假设，即拟胆碱药可增强锥体神经元功能。
